68 research outputs found

    Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections

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    Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples

    Unraveling the Nexus: Exploring the Pathways to Combined Resource Use

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    In response to the unprecedented decline in global natural resource endowments, the so-called nexus framework is gaining increasing influence on resource management practices. In this research, we approach the resource nexus through the concept of nexus pathways. Nexus pathways are configurations that resource flows follow along supply chains leading to the combined use of two or more resources. Three general types of pathways are identified: direct (on-site use), dependent (one-way supply chains), and interdependent (supply-chain feedbacks). We quantify and compare each pathway by means of multiregional input-output analysis and structural path analysis, and apply this approach to a comparative case study on the water-energy nexus (WEN) in the United States and China. Interdependencies or feedbacks are generally thought to be relevant for the WEN, especially between water and energy sectors. Our economy-wide analysis for both countries indicates, however, that feedbacks neither play an important role in the WEN nor substantially take place between water and energy sectors. The most important feedbacks contribute to less than 1% of total resource use, and these take place mostly between manufacturing sectors. Overall, the studied WEN is mostly driven by dependent pathways and, to a lesser degree, direct resource use. Comparative differences between the two countries are largely explained by differences in economic structure, technology, and resource endowments. Our findings call into question current research and policy focus and suggest greater attention to less complex, but more determining, pathways leading to absolute resource use

    The Tropical Seagrass Halophila stipulacea: Reviewing What We Know From Its Native and Invasive Habitats, Alongside Identifying Knowledge Gaps

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    Halophila stipulacea is a small tropical seagrass, native to the Red Sea, Persian Gulf, and the Indian Ocean. It invaded the Mediterranean Sea 150 years ago as a Lessepsian migrant, but so far has remained in insulated, small populations across this basin. Surprisingly, in 2002 it was reported in the Caribbean Sea, where within less than two decades it spread to most of the Caribbean Island nations and reaching the South American continent. Unlike its invasion of Mediterranean, in the Caribbean H. stipulacea creates large, continuous populations in many areas. Reports from the Caribbean demonstrated the invasiveness of H. stipulacea by showing that it displaces local Caribbean seagrass species. The motivation for this review comes from the necessity to unify the existing knowledge on several aspects of this species in its native and invasive habitats, identify knowledge gaps and develop a critical strategy to understand its invasive capacity and implement an effective monitoring and conservation plan to mitigate its potential spread outside its native ranges. We systematically reviewed 164 studies related to H. stipulacea to create the "Halophila stipulacea database." This allowed us to evaluate the current biological, ecological, physiological, biochemical, and molecular knowledge of H. stipulacea in its native and invasive ranges. Here we (i) discuss the possible environmental conditions and plant mechanisms involved in its invasiveness, (ii) assess the impact of H. stipulacea on native seagrasses and ecosystem functions in the invaded regions, (iii) predict the ability of this species to invade European and transoceanic coastal waters, (iv) identify knowledge gaps that should be addressed to better understand the biology and ecology of this species both in its native and non-native habitats, which would improve our ability to predict H. stipulacea's potential to expand into new areas in the future. Considering the predicted climate change scenarios and exponential human pressures on coastal areas, we stress the need for coordinated global monitoring and mapping efforts that will record changes in H. stipulacea and its associated communities over time, across its native, invasive and prospective distributional ranges. This will require the involvement of biologists, ecologists, economists, modelers, managers, and local stakeholder

    Iron oxide and iron oxyhydroxide nanoparticles impair SARS-CoV-2 infection of cultured cells

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    Background Coronaviruses usually cause mild respiratory disease in humans but as seen recently, some human coronaviruses can cause more severe diseases, such as the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the global spread of which has resulted in the ongoing coronavirus pandemic. Results In this study we analyzed the potential of using iron oxide nanoparticles (IONPs) coated with biocompatible molecules like dimercaptosuccinic acid (DMSA), 3-aminopropyl triethoxysilane (APS) or carboxydextran (FeraSpin™ R), as well as iron oxyhydroxide nanoparticles (IOHNPs) coated with sucrose (Venofer®), or iron salts (ferric ammonium citrate -FAC), to treat and/or prevent SARS-CoV-2 infection. At non-cytotoxic doses, IONPs and IOHNPs impaired virus replication and transcription, and the production of infectious viruses in vitro, either when the cells were treated prior to or after infection, although with different efficiencies. Moreover, our data suggest that SARS-CoV-2 infection affects the expression of genes involved in cellular iron metabolism. Furthermore, the treatment of cells with IONPs and IOHNPs affects oxidative stress and iron metabolism to different extents, likely influencing virus replication and production. Interestingly, some of the nanoparticles used in this work have already been approved for their use in humans as anti-anemic treatments, such as the IOHNP Venofer®, and as contrast agents for magnetic resonance imaging in small animals like mice, such as the FeraSpin™ R IONP. Conclusions Therefore, our results suggest that IONPs and IOHNPs may be repurposed to be used as prophylactic or therapeutic treatments in order to combat SARS-CoV-2 infection.This work was supported by the following Grants: CSIC-COV19-012/012202020E154 funded by the Spanish National Research Council Interdisciplinary Thematic Platform (PTI) Global Health (PTI Salud Global), SGL2103021 funded by the European Commission-NextGenerationEU (Regulation EU2020/2094) through CSIC’s Global Health Platform (PTI Salud Global); PDC2021-120759-100 funded by MCIN/AEI/10. 13039/50110 00110 33 and by the “European Union NextGenerationEU/PRTR”, PID2020-112685RB-100 funded by MCIN/AEI/10. 13039/50110 00110 33, and the “Atracción de Talento Investigador” programme (2017-T1/BMD-5155) funded by the “Comunidad de Madrid”. Y. Portilla was first a predoctoral FPU scholar (FPU15/06170) funded by MCIN/AEI/10. 13039/50110 00110 33 and by “ESF Investing in your future”, then a predoctoral scholar funded by CSIC-COV19-012/012202020E154 and is now a postdoctoral scholar funded by the European Commission-NextGenerationEU (Regulation EU2020/2094) through the CSIC’s Global Health Platform (PTI Salud Global, SGL2103021). D. López-García received a JAE-INTRO 2020 Fellowship from the Spanish National Research Council (CSIC, JAEINT-20-01805). V. Mulens-Arias was a postdoctoral scholar working under a Juan de La Cierva-Incorporación Contract (IJCI-2017-31447) funded by MCIN/AEI/10. 13039/50110 00110 33. N. Daviu is a predoctoral scholar (FPU18/04828) funded by MCIN/AEI/10. 13039/50110 00110 33 and by “ESF Investing in your future”. This research work was performed in the framework of the Nanomedicine CSIC HUB (ref. 202180E048).Peer reviewe

    A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex determining gene in the flatfish Solea senegalensis

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    Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 SNP variants in the follicle stimulating hormone receptor (fshr) consistent with an XX / XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. Fshr displayed differential gene expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 non-synonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis.info:eu-repo/semantics/acceptedVersio

    Evaluación de la calidad vs precio de comprimidos de Metformina de 850mg de producción nacional e importados, comercializados en Paraguay utilizados para el control de diabetes

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    La metformina es un fármaco de primera elección, solo o combinado, en el tratamiento inicial de pacientes con diabetes tipo 2, cuya prevalencia a nivel nacional es de 8,0% en hombres y 8,3% en mujeres, con un gasto anual de 283 USD/persona. El estudio fue realizado con el objetivo de evaluar la calidad fisicoquímica y precio de comprimidos de 850 mg de metformina comercializados en nuestro país. Se analizaron medicamentos de producción nacional e importada, conteniendo 850 mg de metformina HCl, tomando como referencia la Farmacopea de los Estados Unidos (USP 38). Para evaluar la calidad de los productos se realizaron ensayos físicos químicos, además de los perfiles de disolución según el medio propuesto por la USP 38. Los resultados obtenidos se encontraron dentro de las especificaciones de valoración, entre 96% y 101% de metformina y los perfiles de disolución entre 70% y 90% de la cantidad declarada en 20 minutos, con una eficiencia de disolución (EF) entre 58% y 93%, mostrando que no existe diferencia estadísticamente significativa (p=0,41). La variación de precios encontrados fue entre 3,6 USD y 8,4 USD. Los productos analizados pueden ser intercambiables en cuanto a la calidad y los perfiles de disolución in vitro, siendo una herramienta para demostrar intercambiabilidad de productos farmacéuticos, buscando el precio más accesible en el mercado nacional y facilitando el tratamiento adecuado sobre todo para la población de escasos recursos manteniendo la calidad y eficacia del mismo

    Fine-grain population structure and transmission patterns of Mycobacterium tuberculosis in southern Mozambique, a high TB/HIV burden area

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    14 paginas, 5 figuras, 2 tablas.Genomic studies of the Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmission, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. To this end, we conducted a 1 year prospective surveillance-based study in Mozambique. We applied whole-genome sequencing (WGS) to 295 positive cultures. We fully characterized MTBC isolates by phylogenetics and dating evaluation, and carried out a molecular epidemiology analysis to investigate further associations with pre-defined transmission risk factors. The majority of strains (49.5%, 136/275) belonged to lineage (L) 4; 57.8 % of them (159/275) were in genomic transmission clusters (cut-off 5 SNPs), and a strikingly high proportion (45.5%) shared an identical genotype (0 SNP pairwise distance). We found two 'likely endemic' clades, comprising 67 strains, belonging to L1.2, which dated back to the late 19th century and were associated with recent spread among people living with human immunodeficiency virus (PLHIV). We describe for the first time the population structure of MTBC in our region, a high tuberculosis (TB)/HIV burden area. Clustering analysis revealed an unforeseen pattern of spread and high rates of progression to active TB, suggesting weaknesses in TB control activities. The long-term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB-coinfected patients, calls into question the role of HIV in TB transmission.This project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programmes 101001038 (TB-RECONNECT), PID2019-104477RB-I00 from Ministerio de Economía y Competitividad (Spanish Government) (to I.C.). We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the ‘Centro de Excelencia Severo Ochoa 2019–2023’.Programme (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Programme. B.S receives a pre-doctoral fellowship from the Secretariat of Universities and Research, Ministry of Enterprise and Knowledge of the Government of Catalonia and co-funded by European Social Fund (AGAUR).Peer reviewe

    Unravelling the population structure and transmission patterns of Mycobacterium tuberculosis in Mozambique, a high TB/HIV burden country

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    Genomic studies of Mycobacterium tuberculosis complex (MTBC) might shed light on the dynamics of its transmission, especially in high-burden settings, where recent outbreaks are embedded in the complex natural history of the disease. We applied Whole-genome sequencing (WGS) to characterize the local population of MTBC, unravel potential transmission links and evaluate associations with host and pathogen factors. Methods A one-year prospective study was conducted in Mozambique, a high HIV/TB burden country. WGS was applied to 295 positive cultures. We combined phylogenetic, geographical and clustering analysis, and investigated associations between risk factors of transmission. Findings A significant high proportion of strains were in recent transmission (45.5%). We fully characterized MTBC isolates by using phylogenetic approaches and dating evaluation. We found two likely endemic clades, comprised of 67 strains, belonging to L1.2, dating from the late XIX century and associated with recent spread among PLHIV. Interpretation Our results unveil the population structure of MTBC in our setting. The clustering analysis revealed an unexpected pattern of spread and high rates of progression, suggesting the failure of control measures. The long-term presence of local strains in Mozambique, which were responsible for large transmission among HIV/TB coinfected patients, hint at possible coevolution with sympatric host populations and challenge the role of HIV in TB transmission.Ministry of Enterprise and Knowledge (Government of Catalonia & European Social Fund, AGAUR fellowship); European Research Council (ERC) European Union’s Horizon 2020.N
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